The presence of insulin resistance in skeletal muscle in severe post-traumatic and septic states is strongly suggested, not only by recent experimental studies, but also by clinical measurement of peripheral body fuel utilization and metabolite production. This concept supports the view that a fuel deficit in skeletal muscle forces the oxidation of branch chain amino acids which leads to proteolysis and failure of protein synthesis. The secondary release of alanine, lactate, and other glucogenic precursors accounts for the augmented hepatic glucogenesis. Evidence at hand further indicates that, in addition to altered endocrine activity, on or more peptides of molecular weight between 1000 and 10000 may induce this muscle metabolic abnormality. The purpose of this project is to correlate clinical metabolic observations with the results of bioassays designed to test in vivo and in vitro the inhibition of the normal muscle response to insulin by the plasma or plasma fractions from injured or septic patients. A recently developed immunoassay to substances in the "active fraction" will be employed in conjunctton with isoelectric focussing, plasma fractionation, and the bioassays to isolate the "factor" responsible for alteration of metabolism in trauma and sepsis.